This proposal is being submitted as part of a program of training of a Research Scientist Development Award. The aim of this study is to investigate the distribution of glutamate dexarboxylase (GAD), tyrosine hydroxylase (TH), cholecystokinin (CCK), and Leu-Enkephalin (ENK) in the pre-frontal, cingulate, primary motor and visual cortex of monkey and man by means of the indirect peroxidase method for immunocytochemistry. These markers have been chosen because they represent well-knwon transmitter and neuropeptide systems present in cerbral cortex and primary anti-sera raised against them are currently available. Tissues will be processed for both light and electron microscopic evaluation. At the light microscopic level, determination of cell counts of neurones in the six layers of cortex will be made by morphometric analysis. The numbers of immunoreactive neurones for each marker will be expressed as a percentage of the total number of cells determined with Nissl-stained sections. Electron microscopic studies for both unreacted and immunoreacted tissues will be observed for the morphological features of cell bodies positive for a given marker, and the nature of the terminals it receives. Where two separate markers appear to interact, double-labelling immunocytochemistry will be applied. Cerbral cortex from both schizophrenic and Huntington disease brains will also be processed for similar morphometric and immunocytochemical studies at the light, and where feasible, the electron microscopic levels. Data from these pathological conditions associated with cognitive impairment will be compared with that obtained from control human and monkey experiments. The overall integrity of the cortical cytoarchitecture and associated markers will be evaluated for organizational disruptions in the disease state.